Persistence of cortical neuronal activity in the dying brain

We report the presence of cortical electrical activity persisting for about 120 min after cardiac arrest. The general consensus is that interruption of brain blood flow triggers a chain of electrophysiological phenomena: oscillatory activity rises in the first tens of seconds [1], followed by a depression of both oscillatory and spiking activities, and then by a slow spreading depolarization due to the beginning of irreversible degenerative processes at the cellular level [2–4]. The spreading depolarization is characterized by direct current changes that can last up to tens of minutes and it has been described by using coarsegrained electroencephalography and electrocorticography measures. As such, low-amplitude and faster local phenomena might have been missed. To address whether some brain activity at a microscale can persist for longer periods after cardiac arrest, we recorded the intraparenchymal activity in the frontal cortex of an adult male macaque monkey using a multi-electrode miniaturized array to monitor neuronal activities during the standard end of a protocol-established euthanasia procedure. Both local field potentials (LFPs) and multi-unit activities (MUAs) [5] were recorded starting from the deep sedated state (induction by ketamine and medetomidine hydrochloride; mixture isoflurane/oxygen to effect), and well beyond the cardiorespiratory arrest caused by the intravascular bolus injection of pentothal sodium. During the initial deep anaesthesia stage, neuronal activity displayed the typical burst suppression regime with irregular LFP and MUA oscillations (Fig. 1a-b). This activity strongly reduced after cardiac arrest (Fig. 1c). However, after about 20 min, bursts of LFPs re-emerged sparse in time up to about 120 min, each displaying a peak of power at 1–3 Hz in the Fourier spectrograms. Importantly, these bursts were accompanied by a supra- and subthreshold MUA modulations giving rise to a significant time-delayed LFP-MUA coupling (see Fig. 1d). Although confined to a single subject, our results prove that the dying brain at the microscale can show electrophysiological activity for long time after cardiac arrest. Importantly, this activity appears after a period of relative silence and it is characterized by a peculiar temporal relationship between LFP and MUA in several electrodes suggesting a non-local origin. This would require a common synaptic input which in principle could be provided by brainstem structures that are typically more resistant to anoxia [4]. We think that our data contribute in posing fundamental questions about the nature of the transition to the death state. For example, what is the metabolic state associated with this process? Can spontaneous (or artificially induced) enhanced neuromodulation be of help in augmenting the resilience to global ischemia? Our finding outlines the importance of investigating the neurobiology of dying with intraparenchymal high-resolution approaches. This could help in addressing central medical questions like the definition of death, the proper timing and the adequate sedation for organ transplantation, and the development of resuscitation and recovery procedures. Whether this activity is a sign of intact brain processing needs further studies.